X-23785725-G-A

Variant names:

• chrX-23785725-G-A
• NM_002970.4:c.385G>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_002970.4(SAT1):​c.385G>A​(p.Val129Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: SAT1 NM_002970.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.60
• Publications: 0 publications found

Genes affected

SAT1 (HGNC:10540): (spermidine/spermine N1-acetyltransferase 1) The protein encoded by this gene belongs to the acetyltransferase family, and is a rate-limiting enzyme in the catabolic pathway of polyamine metabolism. It catalyzes the acetylation of spermidine and spermine, and is involved in the regulation of the intracellular concentration of polyamines and their transport out of cells. Defects in this gene are associated with keratosis follicularis spinulosa decalvans (KFSD). Alternatively spliced transcripts have been found for this gene.[provided by RefSeq, Sep 2009]

SAT1 Gene-Disease associations (from GenCC):

• systemic lupus erythematosus

  Inheritance: XL Classification: STRONG Submitted by: PanelApp Australia
• pediatric systemic lupus erythematosus

  Inheritance: XL Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.819

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002970.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SAT1	NM_002970.4	MANE Select	c.385G>A	p.Val129Ile	missense	Exon 6 of 6	NP_002961.1	P21673
	SAT1	NR_027783.3		n.674G>A		non_coding_transcript_exon	Exon 7 of 7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SAT1	ENST00000379270.5	TSL:1 MANE Select	c.385G>A	p.Val129Ile	missense	Exon 6 of 6	ENSP00000368572.4	P21673
	SAT1	ENST00000379254.5	TSL:3	c.301G>A	p.Val101Ile	missense	Exon 5 of 5	ENSP00000368556.1	E9PD37
	SAT1	ENST00000462639.1	TSL:2	n.341G>A		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 23

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.61
BayesDel_addAF	Uncertain	0.027	T
BayesDel_noAF	Benign	-0.20
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.97	D
M_CAP	Pathogenic	0.52	D
MetaRNN	Pathogenic	0.82	D
MetaSVM	Uncertain	-0.17	T
MutationAssessor	Pathogenic	3.2	M
PhyloP100		9.6
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.92	N
REVEL	Uncertain	0.43
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0080	D
Polyphen		0.99	D
Vest4		0.51
MutPred		0.86		Loss of sheet (P = 0.302)
MVP		0.81
MPC		2.0
ClinPred		0.93	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.59
gMVP		0.90
Mutation Taster		=66/34	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chrX-23803842;